title: Glibenclamide-sensitive mechanism is involved in helodermin-produced vasodilatation in rat mesenteric artery.
abstract: Helodermin-caused vascular relaxation was simultaneously measured with intracellular Ca2+ concentration ([Ca2+]i) in rat mesenteric artery. Helodermin caused concentration-dependent relaxation in the mesenteric artery preconstricted with norepinephrine (NE). Helodermin-caused relaxation was accompanied by decrease in [Ca2+]i, D-cis-Diltiazem, a Ca2+ channel blocker, also lowered the [Ca2+]i and tension increased by NE. However, helodermin relaxed the artery more efficiently than D-cis-diltiazem, suggesting that the peptide decreased myofilament Ca2+ sensitivity. The vascular relaxation and the corresponding decrease in [Ca2+]i induced by helodermin were partly, but significantly attenuated by glibenclamide. Helodermin-induced vascular responses were mimicked by vasoactive intestinal polypeptide (VIP) or forskolin. Furthermore, helodermin increased cAMP contents in the mesenteric artery. These findings show that vasodilatation induced by helodermin is attributable to lowered [Ca2+]i of arterial smooth muscle partly through the activation of glibenclamide-sensitive K+ channels, and to decrease in the myofilament Ca2+ sensitivity. The increase in the cellular cAMP content probably plays a key role in the peptide-induced vasorelaxation.
authors.affiliation: Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: N
authors.initials: N
authors.lastname: Horikawa
authors.forename: H
authors.initials: H
authors.lastname: Ishiro
authors.forename: K
authors.initials: K
authors.lastname: Kataha
authors.forename: T
authors.initials: T
authors.lastname: Nakazawa
authors.forename: N
authors.initials: N
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Ishii
authors.forename: K
authors.initials: K
authors.lastname: Nakayama
authors.forename: N
authors.initials: N
authors.lastname: Yanaihara
authors.forename: K
authors.initials: K
authors.lastname: Shigenobu
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007537:Isometric Contraction / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D015221:Potassium Channels; D009569:Nitric Oxide; C040442:heliodermin; D000242:Cyclic AMP; D010741:Phospholipases A; D005905:Glyburide